Department of Gastroenterology, International University of Health and Welfare Hospital, 537-3 Iguchi, Nasushiobara, Tochigi 329-2763, Japan.
J Clin Biochem Nutr. 2009 Sep;45(2):241-7. doi: 10.3164/jcbn.09-42. Epub 2009 Aug 28.
The present study was undertaken to evaluate the effects of lansoprazole (LPZ) on lipopolysaccharide (LPS)-stimulated toll-like receptor 4 (TLR4) signal transduction systems using the 293hTLR4/MD2-CD14 cells. The cells were incubated and then divided into the following groups: (a) untreated group, (b) non-LPZ treated (1h) group, (c) LPZ-treated (1h) plus non LPS-stimulated (1h) group, (d) LPZ-treated (1h) plus non LPS-stimulated (6h) group, (e) LPZ-treated (1h) plus LPS-stimulated (1h) group, (f) LPZ-treated (1h) plus LPS-stimulated (6h) group, (g) non LPZ-treated (1h) plus LPS-stimulated (1h) group and (h) non LPZ-treated (1h) plus LPS-stimulated (6h) group. Samples from each group were subjected to western blotting for analysis of IkB phosphorylation, intranuclear transfer of NF-kB, phosphorylation of MAP kinase (MAPK), intranuclear transfer of interferon regulatory factor 5 (IRF5), and expression of suppressor of cytokine signaling-1 (SOCS1). In the LPZ-treated groups, neither phosphorylation of MAPK nor intranuclear transfer of IRF5 was suppressed under stimulation with LPS, and enhanced intranuclear transfer of NF-kB and increased expression of SOCS1 were noted by comparison with the group treated with LPS alone. These results suggest that LPZ stimulates the expression of SOCS1 and regulates protein phosphorylation through its activity on TLR4 signal transduction under LPS stimulation.
本研究旨在使用 293hTLR4/MD2-CD14 细胞评估兰索拉唑(LPZ)对脂多糖(LPS)刺激的 toll 样受体 4(TLR4)信号转导系统的影响。将细胞孵育并分为以下几组:(a)未处理组,(b)未用 LPZ 处理(1h)组,(c)用 LPZ 处理(1h)+未用 LPS 刺激(1h)组,(d)用 LPZ 处理(1h)+未用 LPS 刺激(6h)组,(e)用 LPZ 处理(1h)+ LPS 刺激(1h)组,(f)用 LPZ 处理(1h)+ LPS 刺激(6h)组,(g)未用 LPZ 处理(1h)+ LPS 刺激(1h)组,(h)未用 LPZ 处理(1h)+ LPS 刺激(6h)组。对每组样品进行 Western blot 分析,以检测 IkB 磷酸化、NF-kB 核内转移、MAP 激酶(MAPK)磷酸化、干扰素调节因子 5(IRF5)核内转移和细胞因子信号转导抑制因子 1(SOCS1)的表达。在 LPZ 处理组中,与单独用 LPS 处理的组相比,LPS 刺激下 MAPK 磷酸化和 IRF5 核内转移均未受到抑制,并且 NF-kB 的核内转移增强,SOCS1 的表达增加。这些结果表明,LPZ 在 LPS 刺激下通过其对 TLR4 信号转导的活性刺激 SOCS1 的表达,并调节蛋白磷酸化。